Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8P3HMP)

DOT Name	Proenkephalin-A (PENK)
Gene Name	PENK
Related Disease	Advanced cancer ( ) Narcolepsy ( ) Narcolepsy type 1 ( ) Prostate carcinoma ( ) Adenocarcinoma ( ) Alcohol use disorder ( ) Alzheimer disease ( ) Amyotrophic lateral sclerosis type 1 ( ) Analgesia ( ) Autism ( ) Bipolar disorder ( ) Bladder cancer ( ) Bone cancer ( ) Bone osteosarcoma ( ) Cardiac failure ( ) Colorectal carcinoma ( ) Congestive heart failure ( ) Dystonia ( ) Familial amyotrophic lateral sclerosis ( ) Gastric cancer ( ) Hepatocellular carcinoma ( ) Heroin dependence ( ) Herpes simplex infection ( ) Huntington disease ( ) Knee osteoarthritis ( ) Myocardial ischemia ( ) Neuralgia ( ) Neuroblastoma ( ) Parkinson disease ( ) Pheochromocytoma ( ) Prostate neoplasm ( ) Schizophrenia ( ) Small lymphocytic lymphoma ( ) Small-cell lung cancer ( ) Spinal disease ( ) Tuberculosis ( ) Urinary bladder cancer ( ) Urinary bladder neoplasm ( ) Breast cancer ( ) Breast carcinoma ( ) Chronic kidney disease ( ) Neoplasm ( ) Pancreatic cancer ( ) Nervous system disease ( ) Prostate cancer ( )
UniProt ID	PENK_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1PLW; 1PLX; 2LWC; 5E33; 5E3A
Pfam ID	PF01160
Sequence	MARFLTLCTWLLLLGPGLLATVRAECSQDCATCSYRLVRPADINFLACVMECEGKLPSLK IWETCKELLQLSKPELPQDGTSTLRENSKPEESHLLAKRYGGFMKRYGGFMKKMDELYPM EPEEEANGSEILAKRYGGFMKKDAEEDDSLANSSDLLKELLETGDNRERSHHQDGSDNEE EVSKRYGGFMRGLKRSPQLEDEAKELQKRYGGFMRRVGRPEWWMDYQKRYGGFLKRFAEA LPSDEEGESYSKEVPEMEKRYGGFMRF
Function	[Met-enkephalin]: Neuropeptide that competes with and mimic the effects of opiate drugs. They play a role in a number of physiologic functions, including pain perception and responses to stress; [Leu-enkephalin]: Neuropeptide that competes with and mimic the effects of opiate drugs. They play a role in a number of physiologic functions, including pain perception and responses to stress; [Met-enkephalin-Arg-Phe]: Met-enkephalin-Arg-Phe neuropeptide acts as a strong ligand of Mu-type opioid receptor OPRM1. Met-enkephalin-Arg-Phe-binding to OPRM1 in the nucleus accumbens of the brain increases activation of OPRM1, leading to long-term synaptic depression of glutamate release; [PENK(114-133)]: Increases glutamate release in the striatum and decreases GABA concentration in the striatum; [PENK(237-258)]: Increases glutamate release in the striatum.
KEGG Pathway	Neuroactive ligand-receptor interaction (hsa04080 )
Reactome Pathway	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426 ) G alpha (i) signalling events (R-HSA-418594 ) Post-translational protein phosphorylation (R-HSA-8957275 ) Peptide ligand-binding receptors (R-HSA-375276 )

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Advanced cancer	DISAT1Z9	Definitive	Genetic Variation	[1]
Narcolepsy	DISLCNLI	Definitive	Biomarker	[2]
Narcolepsy type 1	DISH7Y6Q	Definitive	Biomarker	[2]
Prostate carcinoma	DISMJPLE	Definitive	Biomarker	[3]
Adenocarcinoma	DIS3IHTY	Strong	Posttranslational Modification	[4]
Alcohol use disorder	DISMB65Y	Strong	Biomarker	[5]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[6]
Amyotrophic lateral sclerosis type 1	DIS5A2M0	Strong	Biomarker	[7]
Analgesia	DISK3TVI	Strong	Biomarker	[8]
Autism	DISV4V1Z	Strong	Biomarker	[9]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[10]
Bladder cancer	DISUHNM0	Strong	Biomarker	[11]
Bone cancer	DIS38NA0	Strong	Genetic Variation	[12]
Bone osteosarcoma	DIST1004	Strong	Genetic Variation	[12]
Cardiac failure	DISDC067	Strong	Altered Expression	[13]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[14]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[13]
Dystonia	DISJLFGW	Strong	Biomarker	[15]
Familial amyotrophic lateral sclerosis	DISWZ9CJ	Strong	Biomarker	[7]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[16]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[17]
Heroin dependence	DISQ1H57	Strong	Biomarker	[18]
Herpes simplex infection	DISL1SAV	Strong	Altered Expression	[19]
Huntington disease	DISQPLA4	Strong	Biomarker	[20]
Knee osteoarthritis	DISLSNBJ	Strong	Therapeutic	[21]
Myocardial ischemia	DISFTVXF	Strong	Therapeutic	[22]
Neuralgia	DISWO58J	Strong	Biomarker	[19]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[23]
Parkinson disease	DISQVHKL	Strong	Altered Expression	[24]
Pheochromocytoma	DIS56IFV	Strong	Altered Expression	[25]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[26]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[27]
Small lymphocytic lymphoma	DIS30POX	Strong	Altered Expression	[28]
Small-cell lung cancer	DISK3LZD	Strong	Altered Expression	[29]
Spinal disease	DISQRITY	Strong	Biomarker	[30]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[31]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[11]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[11]
Breast cancer	DIS7DPX1	moderate	Biomarker	[32]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[32]
Chronic kidney disease	DISW82R7	moderate	Biomarker	[33]
Neoplasm	DISZKGEW	moderate	Altered Expression	[34]
Pancreatic cancer	DISJC981	moderate	Posttranslational Modification	[35]
Nervous system disease	DISJ7GGT	Limited	Therapeutic	[36]
Prostate cancer	DISF190Y	Limited	Biomarker	[3]
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⏷ Show the Full List of 45 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

8 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Proenkephalin-A (PENK).	[37]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Proenkephalin-A (PENK).	[38]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Proenkephalin-A (PENK).	[39]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Proenkephalin-A (PENK).	[40]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Proenkephalin-A (PENK).	[41]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Proenkephalin-A (PENK).	[42]
Amphetamine	DMSZQAK	Approved	Amphetamine decreases the expression of Proenkephalin-A (PENK).	[42]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Proenkephalin-A (PENK).	[44]
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⏷ Show the Full List of 8 Drug(s)

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Proenkephalin-A (PENK).	[43]
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References

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